BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with significant metabolic and hormonal dysregulation. Marjoram (Origanum majorana L.), known for its medicinal properties, has potential in managing PCOS through various bioactive compounds. OBJECTIVE: This study aims to evaluate the effects of marjoram on PCOS symptoms using serum pharmacochemistry, network pharmacology, and molecular docking in a DHEA-induced rat model. METHODS: Polycystic Ovary Syndrome (PCOS) was induced in rats using dehydroepiandrosterone (DHEA). Marjoram's therapeutic effects were evaluated by analyzing oxidative stress biomarkers, hormone levels, and ovarian histopathology. Untargeted serum metabolomics, conducted with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC TQD-MS/MS), identified key bioactive compounds. These compounds were then examined through network pharmacology to map their interactions with PCOS-related pathways, with findings validated via molecular docking. RESULTS: Marjoram treatment significantly reduced oxidative stress by decreasing nitric oxide (NO) and increasing total antioxidant capacity (TAC). Hormonal analysis revealed that high-dose marjoram (100 mg/kg) normalized progesterone, estradiol, testosterone and FSH levels. Body weight gain was also reduced with marjoram treatment, especially at the higher dose. Histopathological evaluation showed fewer ovarian cysts and improved follicular structure with marjoram administration. Network pharmacology analysis highlighted the steroid hormone biosynthesis and estrogen signaling pathways as critical targets, with apigenin and oleic acid identified as active compounds. Molecular docking confirmed strong interactions of these compounds with core PCOS-associated proteins, further supporting marjoram's potential in modulating PCOS symptoms. CONCLUSION: This study reveals that marjoram contains a diverse range of active compounds that can modulate crucial biochemical and histological markers related to PCOS. By combining serum pharmacochemistry with network pharmacology, the research highlights marjoram's potential as a natural supplement to help alleviate PCOS symptoms and slow the syndrome's progression. These findings support further investigation into marjoram's role as a complementary therapy for managing PCOS.